EGFR-TK1-Associated Interstitial Pneumonitis in Nivolumab-Treated Patients with NSCLC: When Is it Worth The Risk?

[摘要] Nivolumab treatment has been shown to increase the risk of epidermal growth factor-tyrosine kinase inhibitors (EGFRTKIs)-associated interstitial pneumonitis (IP) in patients with non-small cell lung cancer (NSCLC) [1]. A higher proportion of IP has been observed for nivolumab in combination with EGFR-TKI versus treatment with either drug alone [1]. Lung cancers represent the principal cause of death cancer-related worldwide with a poor survival rate at five years from diagnosis [2]. Advanced NSCLC has a poor prognosis and receives partial advantage from conventional chemioterapy [1, 2]. In recent years, numerous novel therapies have been introduced for treating advanced NSCLC beyond old chemotherapy and EGFR-TKIs such as erlotinib [2]. Immunotherapy including nivolumab has emerged to result in promising clinical activity in advanced NSCLC [2, 3]. Nivolumab is an immune checkpoint inhibitor that has received the FDA and EMA approval for the treatment of NSCLC in second-line setting [2]. Nivolumab is an anti-programmed cell death-1 (PD-1) monoclonal antibody whose administration may be complicated by immune-related adverse events [1–3]. Nivolumab and EGFR-TKI are currently considered the standard-of-care treatments in NSCLC [1]. However, this therapeutic approach remains controversial given the relatively high incidence of treatment–related toxicities connected with combination of EGFR-TKI and immunotherapy [3]. EGFRTKI has been linked to a significant improvement in clinical outcomes in comparison to chemotherapy in NSCLC patients with sensitizing EGFR gene mutation [3]. However, essentially all patients on therapy with EGFR-TKIs eventually show acquired resistance [3]. It has been detected that activation of the oncogenic EGFR pathway enhances susceptibility of the lung cancers to PD-1 blockade in mouse model, implying that combination of PD-1 blockade with EGFR-TKIs may represent an encouraging therapeutic strategy [3].